A quantitative study of bioenergetics in skeletal muscle lacking utrophin and dystrophin

Muscle energetics and function were investigated in the hindlimb of mice lacking dystrophin (mdx), utrophin and dystrophin (utr-dys) and controls (C57B1/10) using P-31 and H-1 magnetic resonance techniques, electrical nerve stimulation and direct biochemical analysis. At rest, [adenosine triphosphate] and [total creatine] were lowest in utr-dys, while [inorganic phosphate] was elevated. Calculated [adenosine diphosphate] was 3-fold higher in mdx and 5-fold higher in utr-dys than in controls, consistent with an increased adenosine triphosphate requirement for ion pump activity. During stimulation, force production was low only in utr-dys, and this was reflected in the bioenergetic changes. Initial recovery rates of [phosphocreatine] and [adenosine diphosphate] after stimulation were rapid in all groups, indicative of normal mitochondrial adenosine triphosphate production in utr-dys and mdx. Recovery of pH was slow in utr-dys. The data indicate that the severe abnormalities which are present in the absence of utrophin and dystrophin leave basic muscle energetics intact and appear confined to processes involving the sarcolemma. (C) 2002 Elsevier Science B.V. All fights reserved.